The claimed invention relates generally to medical devices and procedures and more particularly to devices and methods for treating defects in the tissue of a living being.
To better treat our aging population, physicians are looking for new and better products and methods to enhance the body's own mechanism to produce rapid healing of musculoskeletal injuries and degenerative diseases. Treatment of these defects has traditionally relied upon the natural ability of these types of tissue to repair themselves. In many instances the body is unable to repair such defects in a reasonable time, if at all. Advances in biomaterials has allowed for the creation of devices to facilitate wound healing in both bone and soft tissues defects and injuries. Such devices are used in tissue regeneration as tissue (e.g. bone) graft scaffolds, for use in trauma and spinal applications, and for the delivery of drugs and growth factors.
Bone and soft tissue repair is necessary to treat a variety of medical (e.g., orthopedic) conditions. For example, when hard tissue, such as bone, is damaged as a result of disease or injury, it is often necessary to provide an implant or graft to augment the damaged bone during the healing process to prevent further damage and stimulate repair. Such implants may take many forms (e.g. plugs, putties, rods, dowels, wedges, screws, plates, etc.) which are placed into the tissue. Typically, such implants can be rigid, flexible, deformable, or flowable and can be prepared in a variety of shapes and sizes. For rigid implants (e.g. bone screws), the defect site is typically preconditioned by forming a depression, channel, or other feature (e.g. pre-tapped hole) therein in preparation for the application of the implant. For non-rigid structural repair materials (e.g. putties and pastes) to be conveniently used, they must be capable of being formed into a variety of complex shapes to fit the contours of the repair site. An accurately configured implant that substantially fills the defect site will enhance the integration of natural bone and tissue to provide better healing over time. For example, when repairing defects in bone, intimate load carrying contact often is desired between the natural bone and the bone substitute material to promote bone remodeling and regeneration leading to incorporation of the graft by host bone.
Current bone graft materials include autografts (the use of bone from the patient), allografts (the use of cadaver bone), and a variety of other artificial or synthetic bone substitute materials. Autografts are typically comprised of cancellous bone and/or cortical bone. Cancellous bone grafts essentially provide minimal structural integrity. Bone strength increases as the implant incorporates surrounding cells and new bone is deposited. For cortical bone, the graft initially provides some structural strength. However, as the graft is incorporated by the host bone, nonviable bone is removed by resorption significantly reducing the strength of the graft. The use of autograft bone may result in severe patient pain and other complications at the harvest site, and there are limitations to the amount of autograft bone that can be harvested from the patient. Allografts are similar to autografts in that they are comprised of cancellous and/or cortical bone with greater quantities and sizes being typically available. Disadvantages of allografts include limited supplies of materials and the potential for transmission of disease. The disadvantages of the existing products creates a need for a better devices and methods for treating defects in the tissue of a living being.
After blood, bone is the most commonly transplanted tissue and autografts/allografts are used in approximately 2.2 million orthopaedic procedures annually. However, the usage of autograft and allograft materials as bone substitutes carries a number of possible complications. In autografts, considered the gold standard in bone substitutes, bone graft material is limited to patient sample availability, and thus is not a suitable candidate material for larger bone defects. For example, an iliac crest bone graft involves a surgical procedure to recover bone and marrow from the patient's iliac crest. Such procedures are associated with chronic pain at the site of graft harvest and a limited volume of autograft, since the iliac crest usually doesn't completely regenerate after harvesting. The issues of donor site morbidity have been reported. Allograft, although more widely available and without the same complications associated with sample harvesting, can result in other complications to the patient, notably disease transmission. Over 96% of FDA recalled allograft tissues were musculoskeletal allografts as a result of contamination, improper donor evaluation, and recipient infections. Additionally, allograft materials have been shown to lack the osteoinductive capacities of autograft samples. Therefore, there exists a need for the development of a synthetic alternative for bone grafts. When considering choices for this type of tissue replacement, a number of key material parameters need to be evaluated. The material would need to be non-toxic, non-immunogenic, capable of bonding with the host bone, capable of supporting in-growth of new bone into the graft, and biodegradable. The graft itself would need also to have adequate surface area contact between the graft and recipient site. While this could be accomplished by modifying the graft site with a reamer, burr or bone shaver, use of these instruments can cause heat generation, which may result in tissue necrosis. An ideal device and process would be one in which the substrate closely mimics natural bone tissue and is deployed in such a manner as to take into consideration the biology of tissue remodeling at the site of injury.
Wound healing in response to injury involves the coordination of a large number of complex cellular and molecular events within the body. This response is defined by the need for cells to respond to signals from the pathologic site, mobilize and migrate to the site of injury, secrete trophic factors, possibly proliferate, promote formation of blood vessels, and, eventually, promote synthesis of extracellular matrix to restore the structure and function of the damaged tissue. These cellular processes are driven by a wide variety of proteins, growth factors, and cytokines that act to control cellular functions. The contribution of cells is often overlooked in biomaterials-based approaches for orthopedic healing, but ultimately cells present at the treatment site, whether transplanted or recruited endogenously, that are responsible for new tissue generation and remodeling. It has recently been reported that many FDA-cleared biomaterials for bone healing are not efficient at retaining cells and, in many instances, were cytotoxic and had pH values less than 7 or greater than 10 when reconstituted. Materials that were not easily soluble (allograft bone and calcium phosphates) were most successful at retaining bone marrow MSCs and inducing osteogenic gene expression in an in vitro simulation of surgical graft preparation.
In addition to the effects of materials on cells, the source and number of cells must be considered. Many in vivo studies combine biomaterials with culture-expanded autologous or allogeneic cells as an implantable graft. Although this is convenient to standardize “doses” of therapeutic agents and seemingly control one variable of the regenerative paradigm, the clinical translation of this lab-oriented approach raises potential regulatory issues with the Food and Drug Administration (FDA) and other agencies. The usage of autologous cells at the point-of-care is an appealing alternative with fewer regulatory requirements and a decreased risk of cell contamination or rejection. A growing amount of data has suggested differences in clinical outcomes in non-union fracture, rotator cuff tear, avascular necrosis, and other orthopedic injuries based on the concentration of MSCs present in bone marrow. The influence of concentration of non-cultured, freshly obtained MSCs on bone formation when combined with HA granular particles is unknown.
Autologous bone grafts are successful because they are comprised of a number of components necessary for tissue regeneration: progenitor cells from the bone marrow, an extracellular matrix to support cellular growth, and osteogenic proteins and growth factors. In order to successfully create new tissue, all three factors need to be integrated, combining both autologous and synthetic materials in order to create an implantable device that elicits normal tissue restoration and achieves full repair.